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Background: Aging is an inevitable biological process. Accelerated aging renders adults more susceptible to chronic diseases and increases their mortality rates. Previous studies have reported the relationship between lifestyle factors and phenotypic aging. However, the relationship between intrinsic factors, such as reproductive factors, and phenotypic aging remains unclear., Methods: This study utilized data from the National Health and Nutrition Examination Survey (NHANES), spanning from 1999 to 2010 and 2015-2018, with 14,736 adult women. Random forest imputation was used to handle missing covariate values in the final cohort. Weighted linear regression was utilized to analyze the relationship between women-specific reproductive factors and PhenoAgeAccel. Considering the potential impact of menopausal status on the results, additional analyses were conducted on premenopausal and postmenopausal participants. Additionally, the Life's Essential 8 (LE8) was used to investigate the impact of healthy lifestyle and other factors on the relationship between women-specific reproductive factors and PhenoAgeAccel. Stratified analyses were conducted based on significant interaction p-values., Results: In the fully adjusted models, delayed menarche and gynecological surgery were associated with increased PhenoAgeAccel, whereas pregnancy history were associated with a decrease. Additionally, early or late ages of menopause, first live birth, and last live birth can all negatively impact PhenoAgeAccel. The relationship between women-specific reproductive factors and PhenoAgeAccel differs between premenopausal and postmenopausal women. High LE8 scores positively impacted the relationship between certain reproductive factors (age at menarche, age at menopause, age at first live birth, and age at last live birth) and phenotypic age acceleration. Stratified analysis showed significant interactions for the following variables: BMI with age at menarche, pregnancy history, and age at menopause; ethnicity with age at menopause, age at first live birth, and parity; smoking status with use of contraceptive pills and gynecologic surgery; hypertension with use of contraceptive pills, pregnancy history, and age at menopause., Conclusion: Delayed menarche, gynecological surgery, and early or late ages of menopause, first live birth, and last live birth are associated with accelerated phenotypic aging. High LE8 score may alleviate the adverse effects of reproductive factors on phenotypic aging., (© 2024. The Author(s).)

Heart failure (HF) remains a significant burden on global healthcare systems, necessitating innovative approaches for its management. This manuscript critically evaluates the role of remote monitoring and telemedicine in revolutionizing HF care delivery. Drawing upon a synthesis of current literature and clinical practices, it delineates the pivotal benefits, challenges, and personalized strategies associated with these technologies in HF management. The analysis highlights the potential of remote monitoring and telemedicine in facilitating timely interventions, enhancing patient engagement, and optimizing treatment adherence, thereby ameliorating clinical outcomes. However, technical intricacies, regulatory frameworks, and socioeconomic factors pose formidable hurdles to widespread adoption. The manuscript emphasizes the imperative of tailored interventions, leveraging advancements in artificial intelligence and machine learning, to address individual patient needs effectively. Looking forward, sustained innovation, interdisciplinary collaboration, and strategic investment are advocated to realize the transformative potential of remote monitoring and telemedicine in HF management, thereby advancing patient-centric care paradigms and optimizing healthcare resource allocation.

A novel five-surface phosphor-in-glass (FS-PiG) structure for high illumination and excellent color uniformity in large-view scale LEDs for sensor light source application is demonstrated. YAG phosphor (Y 3 Al 5 O 12 :Ce 3+ ) was uniformly mixed with ceramic and sintered at 680 °C to form a phosphor wafer. Sophisticated laser engraving was employed on the phosphor wafer to form saddle-shaped large-view scale FS-PiG LEDs. The performance of the FS-PiG LEDs exhibited an illumination of 401 lm, average color temperature (CCT) of 5488 K ± 110 K, and color coordinates (CIE) of (0.3179 ± 0.003, 0.3352 ± 0.003). In contrast to convention single-surface phosphor-in-glass (SS-PiG) LEDs, the performance exhibited an illumination of 380 lm, average CCT of 5830 K ± 758 K, and CIE of (0.3083 ± 0.07, 0.3172 ± 0.07). These indicated that the performance of the FS-PiG LEDs was higher than the SS-PiG LEDs for illumination, CCT, and CIE by 1.7, 7, and 23 times, respectively. Furthermore, the FS-PiG LEDs demonstrate a lower lumen loss of 2% and a reduced chromaticity shift of 5.4 × 10 -3 under accelerated aging at 350 °C for 1008 h, owing to the high ceramic melting temperature of up to 510 °C. In this study, the proposed FS-PiG large-view scale LEDs with excellent optical performance and high reliability may be promising candidates to replace the conventional phosphor-in-organic silicone material used in high-power LEDs for the next generation of sensor light sources, display, and headlight applications.

Though the portfolio of medicines that are extending and improving the lives of patients continues to grow, drug discovery and development remains a challenging business on its best day. Safety liabilities are a significant contributor to development attrition where the costliest liabilities to both drug developers and patients emerge in late development or post-marketing. Animal studies are an important and influential contributor to the current drug discovery and development paradigm intending to provide evidence that a novel drug candidate can be used safely and effectively in human volunteers and patients. However, translational gaps-such as toxicity in patients not predicted by animal studies-have prompted efforts to improve their effectiveness, especially in safety assessment. More holistic monitoring and "digitalization" of animal studies has the potential to enrich study outcomes leading to datasets that are more computationally accessible, translationally relevant, replicable, and technically efficient. Continuous monitoring of animal behavior and physiology enables longitudinal assessment of drug effects, detection of effects during the animal's sleep and wake cycles and the opportunity to detect health or welfare events earlier. Automated measures can also mitigate human biases and reduce subjectivity. Reinventing a conservative, standardized, and traditional paradigm like drug safety assessment requires the collaboration and contributions of a broad and multi-disciplinary stakeholder group. In this perspective, we review the current state of the field and discuss opportunities to improve current approaches by more fully leveraging the power of sensor technologies, artificial intelligence (AI), and animal behavior in a home cage environment., Competing Interests: BB is self-employed as a consultant to TLR Ventures. SB is employed by VeriSIM Life. NB-P and TR are employed by TLR Ventures. C-NL is employed by Pfizer. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Berridge, Baran, Kumar, Bratcher-Petersen, Ellis, Liu and Robertson.)

Ultraviolet B light-emitting diodes (UVB LEDs) hold promise in medical and agricultural applications. The commonly used sapphire substrate for their epitaxy growth possesses a high refractive index and excellent UV light absorption characteristics. However, this high refractive index can induce total internal reflection (TIR) within the substrate, leading to decreased Light Extraction Efficiency (LEE) due to light absorption within the material. In this study, UVB LED chips were detached from the sub-mount substrate and directly affixed onto an aluminum nitride (AlN) substrate with superior heat dissipation using a eutectic process. This was undertaken to diminish packaged thermal resistance (PTR). Simultaneously, optimization of the UVB LED packaging structure was employed to alleviate LEE losses caused by the TIR phenomenon, with the overarching goal of enhancin external quantum efficiency (EQE). The final experimental findings suggest that optimal LEE is achieved with packaging dimensions, including a length (EL L ) of 2 mm, a width (EL W ) of 1.62 mm, and a height (EL H ) of 0.52 mm. At an input current of 200 mA, the output power reaches 50 mW, resulting in an EQE of 6.3%. Furthermore, the packaged thermal resistance from the chip to the substrate surface can be reduced to 4.615 K/W.

A new scheme presents MEMS-based LiDAR with synchronized dual-laser beams for detection range enhancement and precise point-cloud data without using higher laser power. The novel MEMS-based LiDAR module uses the principal laser light to build point-cloud data. In addition, an auxiliary laser light amplifies the single-noise ratio to enhance the detection range. This LiDAR module exhibits the field of view (FOV), angular resolution, and maximum detection distance of 45° (H) × 25° (V), 0.11° (H) × 0.11° (V), and 124 m, respectively. The maximum detection distance is enhanced by 16% from 107 m to 124 m with a laser power of 1 W and an additional auxiliary laser power of 0.355 W. Furthermore, the simulation results show that the maximum detection distance can be up to 300 m with laser power of 8 W and only 6 W if the auxiliary laser light of 2.84 W is used, which is 35.5% of the laser power. This result indicates that the synchronized dual-laser beams can achieve long detection distance and reduce laser power 30%, hence saving on the overall laser system costs. Therefore, the proposed LiDAR module can be applied for a long detection range in autonomous vehicles without requiring higher laser power if it utilizes an auxiliary laser light.

The light distribution of light-emitting diodes (LEDs) generally resembles that of a Lambertian light source. When used as large-area light sources, the light distribution angle of LEDs must be modified through secondary optics design to achieve uniformity and minimize the number of light sources. However, secondary optical components pose several challenges such as demanding alignment accuracy, material aging, detachment, and lower reliability. Therefore, this paper proposes a primary optical design approach to achieve full-angle emission in LEDs without the need for lenses. The design employs a flip-chip as the light source and incorporates a V-shaped packaged structure, including a white wall layer, optical structure layers, and a V-shaped diffuse structure. With this design, the LEDs achieve full-angle emission without relying on lenses. Our experimental results demonstrated a peak intensity angle of 77.7°, a 20.3% decrease in the intensity of the central point ratio, and a full width at half maximum (FWHM) of the light distribution of 175.5°. This design is particularly suitable for thin, large-area, and flexible backlight light sources. Moreover, the absence of secondary optical components allows for a thinner light source module.

Dipterocarpoideae species form the emergent layer of Asian rainforests. They are the indicator species for Asian rainforest distribution, but they are severely threatened. Here, to understand their adaptation and population decline, we assemble high-quality genomes of seven Dipterocarpoideae species including two autotetraploid species. We estimate the divergence time between Dipterocarpoideae and Malvaceae and within Dipterocarpoideae to be 108.2 (97.8‒118.2) and 88.4 (77.7‒102.9) million years ago, and we identify a whole genome duplication event preceding dipterocarp lineage diversification. We find several genes that showed a signature of selection, likely associated with the adaptation to Asian rainforests. By resequencing of two endangered species, we detect an expansion of effective population size after the last glacial period and a recent sharp decline coinciding with the history of local human activities. Our findings contribute to understanding the diversification and adaptation of dipterocarps and highlight anthropogenic disturbances as a major factor in their endangered status., (© 2024. The Author(s).)

Whether transfemoral transcatheter aortic valve replacement (TAVR) can be accomplished in patients with a bicuspid aortic valve (AV) and previous type A aortic dissection remains rarely addressed. We report such a case in whom transfemoral TAVR was smoothly performed employing an extraordinary long sheath to bypass the dissected aortic segment, yet at the cost of perioperative left temporoparietal infarction owing to no suitable cerebral embolic protection device available in the presence of a remaining dissection in the aortic arch. Thus, for such patients, transfemoral TAVR is still feasible but novel embolic protection devices of distinct designs should be developed to avoid perioperative cerebral embolism.

Background: The essential roles of platelets in thrombosis have been well recognized. Unexpectedly, thrombosis is prevalent during thrombocytopenia induced by cytotoxicity of biological, physical and chemical origins, which could be suffered by military personnel and civilians during chemical, biological, radioactive, and nuclear events. Especially, thrombosis is considered a major cause of mortality from radiation injury-induced thrombocytopenia, while the underlying pathogenic mechanism remains elusive., Methods: A mouse model of radiation injury-induced thrombocytopenia was built by exposing mice to a sublethal dose of ionizing radiation (IR). The phenotypic and functional changes of platelets and megakaryocytes (MKs) were determined by a comprehensive set of in vitro and in vivo assays, including flow cytometry, flow chamber, histopathology, Western blotting, and chromatin immunoprecipitation, in combination with transcriptomic analysis. The molecular mechanism was investigated both in vitro and in vivo, and was consolidated using MK-specific knockout mice. The translational potential was evaluated using a human MK cell line and several pharmacological inhibitors., Results: In contrast to primitive MKs, mature MKs (mMKs) are intrinsically programmed to be apoptosis-resistant through reprogramming the Bcl-xL-BAX/BAK axis. Interestingly, mMKs undergo minority mitochondrial outer membrane permeabilization (MOMP) post IR, resulting in the activation of the cyclic GMP-AMP synthase-stimulator of IFN genes (cGAS-STING) pathway via the release of mitochondrial DNA. The subsequent interferon-β (IFN-β) response in mMKs upregulates a GTPase guanylate-binding protein 2 (GBP2) to produce large and hyperreactive platelets that favor thrombosis. Further, we unmask that autophagy restrains minority MOMP in mMKs post IR., Conclusions: Our study identifies that megakaryocytic mitochondria-cGAS/STING-IFN-β-GBP2 axis serves as a fundamental checkpoint that instructs the size and function of platelets upon radiation injury and can be harnessed to treat platelet pathologies., (© 2023. The Author(s).)

We present, what we believe to be, a novel microlens array (MLA) scheme for laser light shaping in laser scanning smart headlight. The laser spot has a Gaussian distribution that may reach a high peak power density in the central part, which is called hot spot. When the laser beam is applied to a phosphor plate for luminous conversion, the hot spot of Gaussian beam causes thermal quench and decreases luminous efficacy. To avoid this effect, an MLA is used, so as to achieve a uniform energy distribution. In this study, we propose a laser scanning smart headlight fabricated by a new MLA structure, with an arrangement providing both light uniformity and shaping. The novel MLA is designed by two-dimensional micro-concave lens array yielding a flat-top beam. The flexible fabrication process employs laser drilling to shape the micro-hole array on the glass substrate surface and then etch it to form MLA without requiring any mask lithography process. The full-width half maximum (FWHM) of light output distribution can be adjusted by the glass etching parameters, and the light distribution could be controlled by the arranged layout of the array. Thus, beams with FWHM divergence ranging from 5° to 34° has been fabricated and characterized. The typical pixel shape is a rectangle with two different FWHMs in two orthogonal directions, and the fabrication method achieves this goal as well. This novel design and unique maskless process of the MLAs is a promising tool for development the next generation laser scanning smart headlight.

Introduction: Wistar Han rats are a preferred strain of rodents for general toxicology and safety pharmacology studies in drug development. In some of these studies, visual functional tests that assess for retinal toxicity are included as an additional endpoint. Although the influence of gender on human retinal function has been documented for more than 6 decades, preclinically it is still uncertain if there are differences in retinal function between naïve male and female Wistar Han rats. Methods: In this study, sex-related differences in the retinal function were quantified by analyzing electroretinography (ERG) in 7-9-week-old ( n = 52 males and 51 females) and 21-23-week-old Wistar Han rats ( n = 48 males and 51 females). Optokinetic tracking response, brainstem auditory evoked potential, ultrasonic vocalization and histology were tested and evaluated in a subset of animals to investigate the potential compensation mechanisms of spontaneous blindness. Results/Discussion: Absence of scotopic and photopic ERG responses was found in 13% of 7-9-week-old (7/52) and 19% of 21-23-week-old males (9/48), but none of female rats (0/51). The averaged amplitudes of rod- and cone-mediated ERG b -wave responses obtained from males were significantly smaller than the amplitudes of the same responses from age-matched females (-43% and -26%, respectively) at 7-9 weeks of age. There was no difference in the retinal and brain morphology, brainstem auditory responses, or ultrasonic vocalizations between the animals with normal and abnormal ERGs at 21-23 weeks of age. In summary, male Wistar Han rats had altered retinal responses, including a complete lack of responses to test flash stimuli (i.e., blindness), when compared with female rats at 7-9 and 21-23 weeks of age. Therefore, sex differences should be considered when using Wistar Han rats in toxicity and safety pharmacology studies with regards to data interpretation of retinal functional assessments., Competing Interests: All authors were employed by Pfizer at the time of the study., (Copyright © 2023 Tyszkiewicz, Hwang, Manickam, Jakubczak, Walters, Bolt, Santos and Liu.)

In recent years, advance care planning (ACP) promotion in Taiwan has expanded beyond clinical practice to the broader population. This study aims to investigate people's attitudes toward ACP and to identify factors influencing their signing of advance directives (ADs) and appointment of health care agents (HCAs)., Methods: We identified 2337 ACP participants from consultation records between 2019 and 2020. The relationships among the participants' characteristics, AD completion, and HCA appointment were investigated., Results: Of 2337 cases, 94.1% completed ADs and 87.8% were appointed HCAs. Welfare entitlement (OR = 0.47, p < 0.001), the place ACP progressed (OR = 0.08, p < 0.001), the participation of second-degree relatives (OR = 2.50, p < 0.001), and the intention of not being a family burden (OR = 1.65, p = 0.010) were significantly correlated with AD completion. The probability of appointing HCAs was higher in participants with family caregiving experience (OR = 1.42, p < 0.05), who were single (OR = 1.49, p < 0.05), and who expected a good death with dignity (OR = 1.65, p < 0.01)., Conclusions: Our research shows that adopting ACP discussion in Taiwan is feasible, which encourages ACP conversation and facilitates AD completion., Implications: Male and younger adults may need extra encouragement to discuss ACP matters with their families., Limitations: due to sampling restrictions, our data were chosen from an urban district to ensure the integrity of the results. Furthermore, interview data could be collected in future research to supplement the quantitative results.

Rodents emit ultrasonic vocalizations (USVs) above the human hearing threshold of ~ 20 kHz to communicate emotional states and to coordinate their social interactive behavior. Twenty-two kHz USVs emitted by adult rats have been reported in a variety of aversive social and behavioral situations. They occur not only under painful or restraining conditions but can also be evoked by gentle cutaneous touch or airflow. This study aimed to test if placement of a human hand in a cage can evoke 22-kHz USVs. It was found that 36% of the adult male Sprague-Dawley and 13% of the adult male Wistar Han rats emitted 22-kHz USVs when a gloved hand was introduced into the cages. Average vocalization onset latencies were 5.0 ± 4.4 s (Sprague-Dawley) and 7.4 ± 4.0 s (Wistar Han) and the USVs had a stable frequency (22 kHz) across the calls, ranging from 0.1 to 2.3 seconds in duration. Surprisingly, no 22-kHz USVs were found in any female Wistar Han rats tested. To further explore the mechanisms underlying this observation, we compared retinal function, basal serum corticosterone, and testosterone levels between the 22-kHz USV responders and non-responders. None of these parameters or endpoints showed any significant differences between the two cohorts. The results suggest that the introduction of a gloved-hand inside the cage can trigger adult male albino rats to emit 22-kHz ultrasonic vocalizations. This response should be considered in USV studies and animal welfare., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Hwang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Although multiple randomized controlled trials (RCTs) and systematic review and meta-analysis were performed to investigate the efficiency and safety of nonsteroidal anti-inflammatory drugs (NSAIDs) and opioids in the treatment of acute renal colic, the therapeutic regimen of renal colic is still controversial. Therefore, the aim of this study was to derive a more concise comparison of the effectiveness and safety between NSAIDs and opioids in the treatment for patients with acute renal colic by a systematic review and meta-analysis. Design: We searched PubMed, Embase, and Cochrane Central Register of controlled trials for seeking eligible studies. The pooled mean difference (MD) or risk ratio (RR) with 95% confidence interval (CI) was calculated using the random effects model. The primary outcome was assessed according to the Grading of Recommendations Assessment, Development and Evaluation. Results: A total of 18 studies involving 3,121 participants were included in the systematic review and meta-analysis. No significant difference between the NSAID and opioid groups was observed, with changes in the visual analog scale (VAS) at 0-30 min (MD = 0.79, 95% CI: -0.51, 2.10). NSAIDs in the form of intravenous administration (IV) had no better effect on the changes in the VAS at 0-30 min, when compared to opioids (MD = 1.25, 95% Cl: -4.81, 7.3). The NSAIDs group in the form of IV had no better outcome compared to the opioids group, as well as the VAS at 30 min (MD = -1.18, 95% Cl: -3.82, 1.45; MD = -2.3, 95% Cl: -5.02, 0.42, respectively). Moreover, similar results of this outcome were also seen with the VAS at 45 min (MD = -1.36, 95% Cl: -5.24, 2.52). Besides, there was a statistical difference in the incidence of later rescue (RR = 0.76, 95% CI: 0.66, 0.89), drug-related adverse events (RR = 0.44, 95% CI: 0.27, 0.71), and vomiting (RR = 0.68, 95% CI: 0.49, 0.96). Conclusion: There is no significant difference between the NSAIDs and opioids in the treatment of renal colic in many outcomes (e.g., the VAS over different periods using different injection methods at 30 and 60 min), which has been focused on in this study. However, the patients who were treated using NSAIDs by clinicians can benefit from fewer side effects., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Leng, Liu, Wang, Peng, Wang and Pan.)

A simple, fast, and reliable method was established for simultaneous determination of 43 pesticides in Schizonepeta tenuifolia . The samples were prepared using solid-phase extraction (SPE) method. Pesticides were extracted from Schizonepeta tenuifolia using acetonitrile, cleaned with Pesticarb/NH 2 , and eluted by mixed solvents of acetonitrile and toluene (3 : 1, v/v). Selected pesticides were identified using DB-35MS capillary column and detected by gas chromatography mass spectrometry. Samples were quantified by external standard method. Recoveries for the majority of pesticides at spike levels of 0.2, 0.5, and 1 mg kg -1 ranged between 70 and 120% (except for Chlorothalonil, Thiamethoxam, and Dicofol), and the relative standard deviations (RSDs n  = 6) were 1.32%-13.91%. Limits of detection (LODs) were 0.0011-0.0135 mg kg -1 , whereas limits of quantification (LOQs) were 0.0038-0.0451 mg kg -1 . The satisfactory accuracy and precision, in combination with a good separation and few interferences, have demonstrated the strong potential of this technique for its application in Schizonepeta tenuifolia analysis., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Guo-wei Zhou et al.)

In oncology research, while xenograft tumor models are easily visualized and humane endpoints can be clearly defined, metastatic tumor models are often based on more subjective clinical observations as endpoints. This study aimed at identifying objective non-invasive criteria for predicting imminent distress and mortality in metastatic lung tumor-bearing mice. BALB/c and C57BL/6 mice were inoculated with CT26 or B16F10 cells, respectively. The mice were housed in Vium smart cages to continuously monitor and stream respiratory rate and locomotion for up to 28 days until scheduled euthanasia or humane endpoint criteria were met. Body weight and body temperature were measured during the study. On days 11, 14, 17 and 28, lungs of subsets of animals were microCT imaged in vivo to assess lung metastasis progression and then euthanized for lung microscopic evaluations. Beginning at day 21, most tumor-bearing animals developed increased respiratory rates followed by decreased locomotion 1-2 days later, compared with the baseline values. Increases in respiratory rate did not correlate to surface tumor nodule counts or lung weight. Body weight measurement did not show significant changes from days 14-28 in either tumor-bearing or control animals. We propose that increases in respiratory rate (1.3-1.5 X) can be used to provide an objective benchmark to signal the need for increased clinical observations or euthanasia. Adoption of this novel humane endpoint criterion would allow investigators time to collect tissue samples prior to spontaneous morbidity or death and significantly reduce the distress of mice in the terminal stages of these metastatic lung tumor models., Competing Interests: The authors have declared that no competing interests exist.

Background: CBA/J mice are standard experimental animals in auditory studies, and age-related changes in auditory pathways are well documented. However, changes in locomotion-related brain regions have not been systematically explored., Results: We showed an increase in immunoreactivity for glial fibrillary acidic protein (GFAP) in the cerebellar molecular layer associated with Purkinje cells in mice at 24 weeks of age but not in the younger mice. Increased GFAP immunoreactivity appeared in the form of clusters and distributed multifocally consistent with hyperplasia of astrocytes that were occasionally associated with Purkinje cell degeneration. Three out of 12 animals at 16 and 24 weeks of age exhibited pre-convulsive clinical signs. Two of these 3 animals also showed increased GFAP immunoreactivity in the cerebellum. Rotarod behavioral assessments indicated decreased performance at 24 weeks of age., Conclusions: These results suggest minimal to mild reactive astrocytosis likely associated with Purkinje cell degeneration in the cerebellum at 24 weeks of age in CBA/J mice. These findings should be taken into consideration prior to using this mouse strain for studying neuroinflammation or aging., (© 2021. The Author(s).)

A novel laser-assisted LED for adaptive-driving-beam (ADB) headlights employing an ultra-reliable Ce 3+ : YAG-based single crystal phosphor (SCP)-converter layer for use in autonomous vehicles is demonstrated. The SCP fabricated at a high-temperature of 1,940°C exhibited better thermal stability than other phosphor-converter materials, evidenced by a thermal aging test. The high-beam pattern of the ADB is measured at a luminous intensity of 88,436 cd at 0°, 69,393 cd at ± 2.5°, and 42,942 cd at ± 5°, which well satisfies the ECE R112 class B regulation. The advantage of introducing the laser-assisted LED system employing the highly reliable SCP is to produce the high intensity for the ADB, which enables the increase of the field of view by 20% and the brightness by 28% for the ADB headlight and results in improving the visibility from ± 7° to ± 8.5° and the illumination distance up to 200 m. This proposed advance ADB headlight with the ultra-reliable SCP and the novel laser-assisted LED is favorable as one of the most promising ADB light source candidates for use in the next-generation autonomous vehicle applications.

Fish morphological phenotypes are important resources in artificial breeding, functional gene mapping, and population-based studies in aquaculture and ecology. Traditional morphological measurement of phenotypes is rather expensive in terms of time and labor. More importantly, manual measurement is highly dependent on operational experience, which can lead to subjective phenotyping results. Here, we developed 3DPhenoFish software to extract fish morphological phenotypes from three-dimensional (3D) point cloud data. Algorithms for background elimination, coordinate normalization, image segmentation, key point recognition, and phenotype extraction were developed and integrated into an intuitive user interface. Furthermore, 18 key points and traditional 2D morphological traits, along with 3D phenotypes, including area and volume, can be automatically obtained in a visualized manner. Intuitive fine-tuning of key points and customized definitions of phenotypes are also allowed in the software. Using 3DPhenoFish, we performed high-throughput phenotyping for four endemic Schizothoracinae species, including Schizopygopsis younghusbandi , Oxygymnocypris stewartii , Ptychobarbus dipogon , and Schizothorax oconnori . Results indicated that the morphological phenotypes from 3DPhenoFish exhibited high linear correlation (>0.94) with manual measurements and offered informative traits to discriminate samples of different species and even for different populations of the same species. In summary, we developed an efficient, accurate, and customizable tool, 3DPhenoFish, to extract morphological phenotypes from point cloud data, which should help overcome traditional challenges in manual measurements. 3DPhenoFish can be used for research on morphological phenotypes in fish, including functional gene mapping, artificial selection, and conservation studies. 3DPhenoFish is an open-source software and can be downloaded for free at https://github.com/lyh24k/3DPhenoFish/tree/master.

Introduction: In pharmacology and toxicology studies, the glomerular filtration rate (GFR) is the gold standard for the assessment of renal function, and the renal clearance of inulin in blood measured by photometers is known as a filtration marker for the determination of GFR. Preclinically, a non-invasive GFR measurement method was recently developed in which near-infrared fluorescently labelled inulin (GFR-Vivo 680) was scanned with fluorescence molecular tomography (FMT). However, measurement of GFR using FMT has major disadvantages and technical challenges, such as requiring experienced skills in animal handling and rapid and precise time management. Additionally, fur and skin pigmentation may severely compromise imaging due to tissue fluorescence absorption. To overcome these drawbacks of FMT imaging, we have developed an in- and ex vivo hybrid method for measuring GFR using the in vivo imaging system (IVIS)., Methods: An IVIS-based imaging method was tested to determine the clearance kinetics of plasma GFR-Vivo 680 after a single bolus injection in conscious C57BL/6 mice administered vehicle or cyclosporine A (CsA, 80 mg/kg) for 14 days., Results: Based on a two-compartment model fitting, the estimated GFR was 235 ± 53 and 189 ± 19 μL/min in vehicle-treated and CsA-treated male mice, respectively (p < 0.01). Our assay revealed the decreased GFR, similar to the sensitivity of FMT imaging, which yielded comparable GFR values (229 ± 61 and 151 ± 35 μL/min in vehicle-treated and CsA-treated mice, respectively, p < 0.01), and to those previously reported in the literature., Discussion: These studies demonstrate the feasibility of IVIS imaging measurement of inulin clearance in untreated, vehicle-treated and cyclosporine A-treated mice. We propose this new method as an alternative, simple, and versatile way to measure GFR in vivo and ex vivo in pharmacological and toxicological studies., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Although maternal deaths are rare in developed regions, the morbidity associated with severe postpartum hemorrhage (SPPH) remains a major problem. To determine the prevalence and risk factors of SPPH, we analyzed data of women who gave birth in Guangzhou Medical Centre for Critical Pregnant Women, which received a large quantity of critically ill obstetric patients who were transferred from other hospitals in Southern China., Methods: In this study, we conducted a retrospective case-control study to determine the prevalence and risk factors for SPPH among a cohort of women who gave birth after 28 weeks of gestation between January 2015 and August 2019. SPPH was defined as an estimated blood loss ≥1000 mL and total blood transfusion≥4 units. Logistic regression analysis was used to identify independent risk factors for SPPH., Results: SPPH was observed in 532 mothers (1.56%) among the total population of 34,178 mothers. Placenta-related problems (55.83%) were the major identified causes of SPPH, while uterine atony without associated retention of placental tissues accounted for 38.91%. The risk factors for SPPH were maternal age < 18 years (adjusted OR [aOR] = 11.52, 95% CI: 1.51-87.62), previous cesarean section (aOR = 2.57, 95% CI: 1.90-3.47), history of postpartum hemorrhage (aOR = 4.94, 95% CI: 2.63-9.29), conception through in vitro fertilization (aOR = 1.78, 95% CI: 1.31-2.43), pre-delivery anemia (aOR = 2.37, 95% CI: 1.88-3.00), stillbirth (aOR = 2.61, 95% CI: 1.02-6.69), prolonged labor (aOR = 5.24, 95% CI: 3.10-8.86), placenta previa (aOR = 9.75, 95% CI: 7.45-12.75), placenta abruption (aOR = 3.85, 95% CI: 1.91-7.76), placenta accrete spectrum (aOR = 8.00, 95% CI: 6.20-10.33), and macrosomia (aOR = 2.30, 95% CI: 1.38-3.83)., Conclusion: Maternal age < 18 years, previous cesarean section, history of PPH, conception through IVF, pre-delivery anemia, stillbirth, prolonged labor, placenta previa, placental abruption, PAS, and macrosomia were risk factors for SPPH. Extra vigilance during the antenatal and peripartum periods is needed to identify women who have risk factors and enable early intervention to prevent SPPH.

High color rendering index (CRI) and wide correlated color temperatures (CCTs) white LEDs (WLEDs) employing CaAlSiN 3 : Eu 2+ and Lu 3 Al 5 O 12 : Ce 3+ co-doped phosphor-in-glass (PiG) are demonstrated. Through fabrication using a low sintering temperature of 620°C to minimize inter-diffusion between the red phosphor and glass, and adjusting thickness of 0.5-0.7 mm to obtain the chromaticity tailorable co-doped PiG, the WLEDs exhibit high CRI of 94 and wide CCTs of 3900 K to 5300 K. This CRI is the highest yet reported for the co-doped PiG. The proposed of the co-doped PiG with good thermal stability fabricated by using a low sintering temperature may provide a novel technique to achieve high-performance WLEDs with high CRI for use in many high-quality of indoor lighting applications, especially in color inspection, clinical inspection, and gallery lighting.

Objective: The aim of this study was to retrospectively evaluate the feasibility and safety of high-intensity focused ultrasound (HIFU) treatment as the preoperative management of cesarean scar pregnancy (CSP)., Materials and Methods: 225 patients with definite Type I CSP were treated with suction curettage under hysteroscopic guidance. Among them, 103 patients chose HIFU treatment before hysteroscopy (assign to the HIFU group), and the other 122 patients without any pretreatment before hysteroscopy to the control group. The successful rate, volume of intraoperative blood loss, time for serum β-human chorionic gonadotropin (β-hCG) level returned to normal, gestational sac disappeared, normal menstrual recovery, and adverse effects were collected and analyzed to compare the two approaches., Results: The successful rate (98.06%) in the HIFU group was higher than that (91.80%) in the contrast group. The median ablation time was 39 min and the median HIFU sonication time was 106.6 s. The median volume of intraoperative blood loss in the HIFU group was lower than that in the contrast group (P < 0.001), and the median time of gestational sac disappeared in the HIFU group was shorter than that in the contrast group. There were no statistically significant differences in the time of serum β-hCG returned to normal and days of menstrual recovery between the 2 groups., Conclusion: Based on our results, it appears that HIFU ablation is a safe and effective modality as pre-treatment before hysteroscopy in the management of CSP., (Copyright © 2020. Published by Elsevier B.V.)

The potential for neurogenesis in the cranial (superior) cervical ganglia (SCG) of the sympathetic nervous system was evaluated. Eleven consecutive daily doses of guanethidine (100 mg/kg/d) were administered intraperitoneally to rats in order to destroy postganglionic sympathetic neurons in SCG. Following the last dose, animals were allowed to recover 1, 3, or 6 months. Right and left SCG from guanethidine-treated and age-matched, vehicle-treated control rats were harvested for histopathologic, morphometric, and stereologic evaluations. Both morphometric and stereologic evaluations confirmed neuron loss following guanethidine treatment. Morphometric analysis revealed a 50% to 60% lower number of tyrosine hydroxylase (TH)-positive neurons per unit area of SCG at both 3 and 6 months of recovery, compared to ganglia of age-matched controls, with no evidence of restoration of neuron density between 3 and 6 months. Reductions in TH-positive neurons following guanethidine treatment were corroborated by unbiased stereology of total hematoxylin and eosin-stained neuron numbers in SCG. Stereologic analyses revealed that total neuron counts were lower by 37% at 3 months of recovery when compared to age-matched vehicle controls, again with no obvious restoration between 3 and 6 months. Thus, no evidence was found that postganglionic neurons of the sympathetic nervous system in the adult rat have a neurogenic capacity.

A new scheme of LiDAR-embedded smart laser headlight module (LHM) for autonomous vehicles is proposed and demonstrated. The LiDAR sensor was fabricated by LeddarTech with the wavelength of 905-nm, whereas the LHM was fabricated by a highly reliable glass phosphor material that exhibited excellent thermal stability. The LHM consisted of two blue laser diodes, two blue LEDs, a yellow glass phosphor-converter layer with a copper thermal dissipation substrate, and a parabolic reflector to reflect the blue light and the yellow phosphor light combined into white light. The LHM exhibited a total output optical power of 9.5 W, a luminous flux of 4,000 lm, a relative color temperature of 4,300 K, and an efficiency of 421 lm/W. The high-beam patterns of the LHMs were measured to be 180,000 luminous intensity (cd) at 0° (center), 84,000 cd at ± 2.5°, and 29,600 cd at ± 5°, which met the ECE R112 class B regulation. The low-beam patterns also satisfied the ECE R112 class B regulation as well. Integrating the signals received from the Lidar detection and CCD image by a smart algorithm, we demonstrated the generation of smart on/off signals for controlling the laser headlights. The recognition rate of the objects was evaluated to be more than 86%. This novel LiDAR-embedded smart LHM with the unique highly reliable glass phosphor-converter layer is favorable as one of the most promising candidates for use in the next-generation high-performance autonomous vehicle applications.

Background: Equity in medical resource utilization is a crucial concern in countries with national health insurance systems. From the perspective of an active aging framework, public health insurance is one of the pillars of economic security, as suggested by the World Bank, to achieve the goal of social security for older adults. This study thus sought to quantify income-related inequality in national health insurance systems, especially during the global economic crisis of 2007-2008., Methods: By employing the Taiwan National Health Interview Surveys (2005 and 2009) datasets, we analyzed the socioeconomic inequality of outpatient service utilization for older Taiwanese adults during the financial crisis of 2007-2008. We used corrected concentration indices (CCIs) to examine inequalities over time. Furthermore, we decomposed socioeconomic inequalities to reveal the contributions of determinant factors. The dependent variables related to whether participants had used outpatient services in the previous month, and the independent factors included individual's needs, enabling, predisposing, and environmental factors proposed by Andersen model., Results: The sample consisted of 2415 observations in 2005 and 2554 observations in 2009. The income-related health care inequality was minor from pro-rich to pro-poor across the study duration, although the difference was insignificant (women: from a concentration index [CI] of 0.0256 in 2005 to a CI of - 0.0098 in 2009; men: from a CI of 0.0379 in 2005 to a CI of 0.0310 in 2009). We used a probit model to analyze the effect of explanatory factors on outpatient resource utilization by men and women. After other factors were controlled for, we found that that the income variable had a positive and significant effect on outpatient service utilization in 2009 and the absolute contribution of income to inequality notably increased from 0.0480 in 2005 to 0.3247 in 2009 for older women., Conclusions: In conclusion, Taiwan's National Health Insurance system guarantees the accessibility of health care services to older adults, but slight income-related inequality was maintained in the outpatient resource utilization of women during the 2007-2008 financial crisis. Close attention should be paid to the vulnerability of women during times of economic insecurity.

This retracts the article entitled, "Effects of Sodium Lighting on Circadian Rhythms in Rats" by Xian Chen, Chang-Ning Liu, and Judith E Fenyk-Melody published in the May issue vol 58, issue 3, p 311-320. 1 This article is being retracted with the support of all 3 coauthors due to methodological and authorship issues.

Background: Acute pancreatitis (AP) is associated with high complications. Early, reliable prediction of mortality may improve patient management., Methods: We retrospectively reviewed medical records of 1,599 patients with AP treated at a single large hospital in southwest China. Models to predict mortality were derived from a subset of 1,062 patients (development dataset), and the models were then validated in the remaining 537 patients (validation dataset). Independent risk factors and prediction models for mortality were identified using logistic regression., Results: A total of 33 patients in the development dataset and 13 in the validation dataset died during hospitalization. Independent risk factors for mortality were found to be plasma urea levels, glucose levels and platelet counts at admission; as well as peak urea levels, leukocyte counts and use of invasive ventilation during hospitalization. Based on the development dataset, a mortality prediction model based only on urea level at admission gave an area under the curve (AUC) of 0.81, which did not significantly improve by incorporating glucose level or platelet count at admission. Significantly better was a model taking into account three in-hospital parameters: peak urea level, leukocyte count and use of invasive ventilation (AUC 0.97)., Conclusions: While mortality of AP patients can be predicted reasonably well based only on urea values at admission, predictions are more reliable when they take into account in-hospital data on peak urea level, leukocyte count and use of invasive ventilation., Competing Interests: The authors have declared that no competing interests exist.

Rodent studies often must be conducted during an animal's active phase (that is, in darkness) yet also during a typical day shift for staff. Low-pressure sodium lighting (LPSL), to which human retinas are more sensitive than rodents' at low intensity, has been used to facilitate study conduct in dark phase. The assumption was that LPSL would be equivalent to total darkness due to low rodent retinal sensitivity but provide enough lighting for safe technical manipulations due to higher human retinal sensitivity. Unlike other light sources, LPSL has been tested for effects on circadian rhythm specific to locomotive activities in albino mice. Whether LPSL affects circadian rhythms in rats is unknown. In this study, circadian endpoints were derived from body temperature and locomotor activity via telemeters in 8 adult male Wistar rats. When moved from a 12:12-h white-light (that is, cold white fluorescent light):dark (LD) cycle to a 12:12-h white-light:sodium-light cycle, rats demonstrated free-running and disrupted circadian rhythms (that is, lengthened circadian period and reduced circadian robustness and amplitude). Body temperature and locomotor activity were significantly lower in the LPSL phase as compared with dark phase under the baseline condition. When exposed to a 12:12 h sodium-light:dark (SD) cycle, rats entrained with a circadian period similar to 12:12-h white-light:dark (LD), but significantly different from the period under constant darkness (DD). Circadian onset and acrophase were delayed under SD compared with LD. When illuminated with a LPSL pulse under DD, rats showed phase shifts similar to white-light pulse effects, consistent with the phase response curve. To determine whether the image-forming photoreceptors are involved in this process, we used electroretinography. Compared with white light, 589-nm light generated during electroretinography elicited rod photoreceptors responses with longer latency and cone photoreceptor responses with lower amplitude. These results indicate that LPSL is a weaker zeitgeber than white light and may alter the circadian system in rats. Furthermore, because LPSL appeared to be visible to rats, it may not be an appropriate substitute for actual darkness.

In drug discovery and development, X-ray micro-computed tomography (micro-CT) has gained increasing importance over the past decades. In recent years, micro-CT imaging of soft tissues has become popular due to the introduction of a variety of radiopaque contrast agents. More recently, nanoparticle-based ExiTron nano 12,000 has become commercially available for the nonclinical micro-CT imaging of soft tissues in rodents. Phagocytosis and accumulation of the contrast agent by Kupffer cells in the liver, as well as macrophages in the spleen, increase the soft tissue X-ray attenuation for up to 6 months. Therefore, it is essential to understand the potential toxicity of this nanomaterial in micro-CT imaging prior to its application in pharmacology and/or toxicology studies. Herein, we describe the time-course and distribution of the contrast in the liver, spleen and blood after a single intravenous injection (IV) of this nanoparticle contrast agent at 0.1 ml/mouse. Thoracic images of male adult C57BL/6 mice were acquired using a Bruker SkyScan 1276 micro-CT over a period of 29 days. The stability of X-ray attenuation enhancement in the above tissues was also tested after a single dose of Kupffer cell toxicant gadolinium chloride (GdCl 3 ) at 15 mg/kg on day 2. The liver, spleen and kidney were examined microscopically on days 15 and 29 post treatment. Serum and liver cytokines (IL-1β, IL-2, IL-6, IL-10, IL-12p70, IFN-γ, IP-10, MIP1-α, MIP1-β and TNF-α) were quantified on days 15 and 29 as indicators of a pro-inflammatory response to treatment. This study determined that there was an accumulation of amphophilic granular material in the cells of the mononuclear phagocyte system in the liver and spleen following a single dose of ExiTron nano 12,000 and a second dose of GdCl 3 or its vehicle. However, ExiTron nano12000 contrast administration did not cause any hepatotoxicity in the liver, nor did pro-inflammatory cytokines release in the liver or serum. Similarly, there were no adverse pathologies in the spleen or kidneys. In summary, ExiTron nano12000 contrast agent-enhanced micro-CT could be used as a safe method in up to 29-day longitudinal efficacy and toxicology mouse studies for the non-invasive assessment of the liver and spleen., (Copyright © 2019 Elsevier Inc. All rights reserved.)

An advanced laser headlight module (LHM) employing highly reliable glass phosphor is demonstrated. The novel glass-based YAG phosphor-converter layers fabricated by low-temperature of 750°C exhibited better thermal stability. The LHM consisted of a 5 × 1 blue laser diode array, an aspherical lens, a glass phosphor-converter layer with an aluminum thermal dissipation substrate, and a dichroic filter to allow pass blue light and reflect yellow phosphor light. The 5 × 1 blue laser array was packaged with five blue lasers having optical power of 1.2 W per laser. The LHM exhibited total output optical power of 6 W, luminous flux of 1860 lm, relative color temperature of 4100 K, and efficiency of more than 310 lm/W. The high-beam patterns of the LHMs were measured to be 45,000 luminous intensity (cd) at 0°, 31,000 cd at ± 2.5°, and 12,500 cd at ± 5°, which were well satisfied the ECE R112 class B regulation. The proposed high-performance LHM with highly reliable glass-based phosphor-converter layer fabricated by low temperature is favorable as one of the promising LHM candidates for use in the next-generation automobile headlight applications.

Chemotherapy-induced peripheral neuropathy (CiPN) is a serious adverse effect in the clinic, but nonclinical assessment methods in animal studies are limited to labor intensive behavioral tests or semi-quantitative microscopic evaluation. Hence, microRNA (miRNA) biomarkers and automated in-life behavioral tracking were assessed for their utility as non-invasive methods. To address the lack of diagnostic biomarkers, we explored miR-124, miR-183 and miR-338 in a CiPN model induced by paclitaxel, a well-known neurotoxic agent. In addition, conventional and Vium's innovative Digital Vivarium technology-based in-life behavioral tests and postmortem microscopic examination of the dorsal root ganglion (DRG) and the sciatic nerve were performed. Terminal blood was collected on days 8 or 16, after 20 mg/kg paclitaxel was administered every other day for total of 4 or 7 doses, respectively, for plasma miRNA quantification by RT-qPCR. DRG and sciatic nerve samples were collected from mice sacrificed on day 16 for miRNA quantification. Among the three miRNAs analyzed, only miR-124 was statistically significantly increased (5 fold and 10 fold on day 8 and day 16, respectively). The increase in circulating miR-124 correlated with cold allodynia and axonal degeneration in both DRG and sciatic nerve. Automated home cage motion analysis revealed for the first time that nighttime motion was significantly decreased (P < 0.05) in paclitaxel-dosed animals. Although both increase in circulating miR-124 and decrease in nighttime motion are compelling, our results provide positive evidence warranting further testing using additional peripheral nerve toxicants and diverse experimental CiPN models., Competing Interests: QP, AS, IP, JF-M, AV, MB, CS, JCC and C-NL are employed by Pfizer. Pfizer paid a scientific service fee to Vium Inc. JM and LS are employed by Vium Inc. There are no patents, products in development or marketed products to declare. This does not alter our adherence to all the PLOS ONE policies on sharing data and materials.

Hemoglobin H (Hb H) disease is usually characterized by the existence of Hb H, which influences the degree of functional anemia. We here report a patient with a rare Hb H disease genotype (- SEA /-α 27.6 ), who was observed to paradoxically have no detectable Hb H fraction on electrophoresis. To date, the reason why the quantity of Hb H component and the clinical presentation in Hb H disease vary widely is still incompletely understood. Our report demonstrates a possible explanation - the different degradation ability of excess β-globin chains, which might be regulated by the 27.6 kb sequence of α-globin gene., (© 2018 by the Association of Clinical Scientists, Inc.)

Background: Cystic echinococcosis (CE) and alveolar echinococcosis (AE) are highly endemic in Xiji County of Ningxia Hui Autonomous Region (NHAR) in China where the control campaign based on dog de-worming with praziquantel has been undertaken over preceding decades. This study is to determine the current prevalence of Echinococcus granulosus and E. multilocularis in domestic dogs and monitor the echinococcosis transmission dynamics., Methods: Study villages were selected using landscape patterns (Geographic Information System, GIS) for Echinococcus transmission "hot spots", combined with hospital records identifying risk areas for AE and CE. A survey of 750 domestic dogs, including copro-sampling and owner questionnaires, from 25 selected villages, was undertaken in 2012. A copro-multiplex PCR assay was used for the specific diagnosis of E. granulosus and E. multilocularis in the dogs. Data analysis, using IBM SPSS Statistics, was undertaken, to compare the prevalence of the two Echinococcus spp. in dogs between four geographical areas of Xiji by the χ 2 test. Univariate analysis of the combinations of outcomes from the questionnaire and copro-PCR assay data was carried out to determine the significant risk factors for dog infection., Results: The highest de-worming rate of 84.0% was found in the northwest area of Xiji County, and significant differences (P <  0.05) in the de-worming rates among dogs from the four geographical areas of Xiji were detected. The highest prevalence (19.7%, 59/300) of E. multilocularis occurred in northwest Xiji, though the highest prevalence (18.1%, 38/210) of E. granulosus occurred in southwest Xiji. There was no significant difference (P >  0.05) in the prevalence of E. granulosus in dogs from the northwest, southwest, northeast, and southeast of Xiji, but there were significant differences (P <  0.05) between dogs infected with E. multilocularis from the four areas. None of the other independent variables was statistically significant., Conclusions: The results from this study indicate a high prevalence of both E. granulosus and E. muiltilocularis in dogs in Xiji County, NHAR. Transmission of E. multilocularis was more impacted by geographical risk-factors in Xiji County than that of E. granulosus. Dogs have the potential to maintain the transmission of both species of Echinococcus within local Xiji communities, and the current praziquantel dosing of dogs appears to be ineffective or poorly implemented in this area.

The seeded Free-Electron Laser (FEL) FERMI is the first source of short-wavelength light possessing the full coherence of optical lasers, together with the extreme power available from FELs. FERMI provides longitudinally coherent radiation in the Extreme Ultraviolet and soft x-ray spectral regions, and therefore opens up wide new fields of investigation in physics. We first propose experiments exploiting this property to provide coherent control of the photoionization of neon and helium, carry out numerical calculations to find optimum experimental parameters, and then describe how these experiments may be realized. The approach uses bichromatic illumination of a target and measurement of the products of the interaction, analogous to previous Brumer-Shapiro-type experiments in the optical spectral range. We describe operational schemes for the FERMI FEL, and simulate the conditions necessary to produce light at the fundamental and second or third harmonic frequencies, and to control the phase with respect to the fundamental. We conclude that a quantitative description of the phenomena is extremely challenging for present state-of-the-art theoretical and computational methods, and further development is necessary. Furthermore, the intensity available may already be excessive for the experiments proposed on helium. Perspectives for further development are discussed.

The purpose of this study was to evaluate functional measures of diminished sympathetic activity after postganglionic neuronal loss in the conscious rat. To produce variable degrees of sympathetic postganglionic neuronal loss, adult rats were treated daily with toxic doses of guanethidine (100mg/kg) for either 5days or 11days, followed by a recovery period of at least 18days. Heart rate, blood pressure, cardiac baroreflex responsiveness, urinalysis (for catecholamine metabolite, 3-methoxy-4-hydroxyphenylethylenglycol; MHPG), and pupillometry were performed during the recovery period. At the end of the recovery period stereology of superior cervical ganglia (SCG) was performed to determine the degree of neuronal loss. Total number of SCG neurons was correlated to physiological outcomes using regression analysis. Whereas guanethidine treatment for 11days caused significant reduction in the number of neurons (15,646±1460 vs. 31,958±1588), guanethidine treatment for 5days caused variable levels of neuronal depletion (26,009±3518). Regression analysis showed that only changes in urinary MHPG levels and systolic blood pressure significantly correlated with reduction of SCG neurons (r 2 =0.45 and 0.19, both p<0.05). Although cardiac baroreflex-induced reflex tachycardia (345.7±19.6 vs. 449.7±20.3) and pupil/iris ratio (0.50±0.03% vs. 0.61±0.02%) were significantly attenuated in the 11-day guanethidine treated rats there was no significant relationship between these measurements and the number of remaining SCG neurons after treatment (p>0.05). These data suggest that basal systolic blood pressure and urinary MHPG levels predict drug-induced depletion of sympathetic activity in vivo., (Copyright © 2017 Elsevier Inc. All rights reserved.)

A novel technique is presented for producing micro-hyperboloid lensed fibers for efficient coupling to semiconductor laser chips. A three-step process including a precision mechanical grinding, a spin-on-glass (SOG) coating and an electrostatic pulling process is used to form the hyperboloid lens structure on a flat-end single mold fiber (SMF) with the core diameter of 6.6 μm. Micro-hyperboloid lensed fibers with tunable radii of curvature around 4.18 - 4.83 μm can be formed on the SMF end face. A high average coupling efficiency around 80% and low coupling variation of 0.116 ± 0.044% are obtained for the produced fibers. The developed method is efficient to produce micro-hyperboloid lensed fibers for high-performance light coupling between the SMF and the semiconductor diode lasers.

Cardiovascular incidences are markedly higher in men than in pre-menstrual women. However, this advantage in women declines with aging and therefore can be correlated with the sex hormone 17β-Estradiol (E2) which is reported to protect heart cells by acting though estrogen receptors (ERs). In this study we have determined the effect of E2/ERβ against ISO induced cellular hypertrophy in H9c2 cardiomyoblast cells. The results confirm that ISO induced cardiac-hypertrophy by elevating the levels of hypertrophy associated proteins, ANP and BNP and further by upregulating p-CaMKII, calcineurin, p-GATA4 and NFATc3 which was correlated with a significant enlargement of the H9c2 cardiomyoblast. However, overexpression of ERβ and/or administration of E2 inhibited ISO-induced hypertrophy in H9c2 cells. In addition, E2/ERβ also inhibited ISO-induced NFATc3 translocation, and reduced the protein level of downstream marker, BNP. Furthermore, by testing with the calcineurin inhibitor (CsA), it was confirmed that calcineurin acted as a key mediator for the anti-hypertrophic effect of E2/ERβ. In cells treated with calcium blocker (BATPA), the inhibitory effect of E2/ERβ on ISO-induced Ca2+ influx and hypertrophic effects were totally blocked suggesting that E2/ERβ inhibited calcineurin activity to activate I-1 protein and suppress PP1, then induce PLB protein phosphorylation and activation, resulting in Ca2+ reuptake into sarcoplasmic reticulum through SR Ca2+ cycling modification. In conclusion, E2/ERβ suppresses the Ca2+ influx and calcineurin activity induced by ISO to enhance the PLB protein activity and SR Ca2+ cycling.

Background: Although some effects of gene-gene interactions on nicotine-dopamine metabolism for smoking behavior have been reported, polymorphisms of cytochrome P450 (CYP) 2A6 and catechol-O-methyltransferase (COMT) have not been studied together to determine their effects on smokers. The aim of this study was to investigate the effects of the interaction between the CYP 2A6 and COMT genes on smoking behavior in young Taiwanese men., Results: A self-report questionnaire regarding smoking status was administered to 500 young men. Polymorphisms of the CYP 2A6 and COMT genes as well as urinary nicotine and urinary cotinine levels were determined. The odds ratio for starting smoking was significantly lower in subjects carrying a CYP2A6 low activity/variant COMT rs4680 genotype than in those possessing a CYP2A6 wild-type/variant COMT rs4680 genotype (0.44, 95% confidence interval = 0.19-0.98, P = 0.043). Comparisons of Fagerstrom Test for Nicotine Dependence (FTND), Physiological Cigarette Dependence Scale (PCDS), and Cigarette Withdrawal symptoms (CWS-21) among the smokers with different CYP2A6/COMT polymorphisms were not significantly different. The adjusted urinary nicotine concentrations were not significantly different between the two groups carrying different genotypes. The adjusted urinary cotinine level was significantly different between the COMT rs4680 wild-type group and COMT rs4680 variant group [92.46 ng/μL vs. 118.24 ng/μL (median value), P = 0.041] and between the COMT rs4680 wild-type/COMT rs165599 variant group and COMT rs4680 variant/COMT rs165599 variant group (97.10 ng/μL vs. 122.18 ng/μL, P = 0.022)., Conclusions: These findings suggest that a single nucleotide polymorphism (rs4680) of the COMT gene and the interaction between the CYP 2A6 and COMT genes affect smoking status in young Taiwanese men.

The goal of this study was to determine the degree of sympathetic postganglionic neuronal loss required to impair cardiovascular-related sympathetic activity. To produce neuronal loss separate groups of rats were treated daily with guanethidine for either 5days or 11days, followed by a recovery period. Sympathetic activity was measured by renal sympathetic nerve activity (RSNA). Stereology of thoracic (T13) ganglia was performed to determine neuronal loss. Despite loss of more than two thirds of neurons in T13 ganglia in both treated groups no effect on resting blood pressure (BP) or heart rate (HR) was detected. Basal RSNA in rats treated for 5days (0.61±0.10μV∗s) and 11days (0.37±0.08μV∗s) was significantly less than vehicle-treated rats (0.99±0.13μV∗s, p<0.05). Increases in RSNA by baroreceptor unloading were significantly lower in 5-day (1.09±0.19μV∗s) and 11-day treated rats (0.59±0.11μV∗s) compared with vehicle-treated rats (1.82±0.19μV∗s, p<0.05). Increases in RSNA to chemoreceptor stimulation were significantly lower in 5-day treated rats (1.54±0.25μV∗s) compared with vehicle-treated rats (2.69±0.23μV∗s, p<0.05). Increases in RSNA in 11-day treated rats were significantly lower (0.75±0.15μV∗s, p<0.05) compared with both vehicle-treated and 5-day treated rats. A positive correlation of neurons to sympathetic responsiveness but not basal activity was detected. These data suggest that diminished capacity for reflex sympathetic responsiveness rather than basal activity alone must be assessed for complete detection of neurophysiological cardiovascular impairment., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Brain development requires a fine-tuned copper homoeostasis. Copper deficiency or excess results in severe neuro-pathologies. We demonstrate that upon neuronal differentiation, cellular demand for copper increases, especially within the secretory pathway. Copper flow to this compartment is facilitated through transcriptional and metabolic regulation. Quantitative real-time imaging revealed a gradual change in the oxidation state of cytosolic glutathione upon neuronal differentiation. Transition from a broad range of redox states to a uniformly reducing cytosol facilitates reduction of the copper chaperone Atox1, liberating its metal-binding site. Concomitantly, expression of Atox1 and its partner, a copper transporter ATP7A, is upregulated. These events produce a higher flux of copper through the secretory pathway that balances copper in the cytosol and increases supply of the cofactor to copper-dependent enzymes, expression of which is elevated in differentiated neurons. Direct link between glutathione oxidation and copper compartmentalization allows for rapid metabolic adjustments essential for normal neuronal function.

Background: Tracheal intubation of laboratory mice remains essential yet challenging for most researchers. The aim of this study was to investigate whether this procedure can be more efficiently and safely accomplished by a novel method using slim and torqueable guidewires to guide access to the trachea., Methods: This study was carried out in an animal laboratory affiliated to a tertiary medical center. Mice weighing 22 to 28 g were subjected to various open-chest experiments after being anesthetized with intraperitoneal ketamine (100 mg/kg) and lidocaine hydrochloride (10 mg/kg). The oropharyngeal cavity was opened with angled tissue forceps, and the trachea was transilluminated using an external light. The vocal cords were then crossed using either the Conventional method with a 38-mm-long, end-blunted stiff needle as a guide for insertion of a 22-gauge, 25-mm-long intravenous catheter into the trachea, or the Modified method utilizing using a 0.014-inch-thin torqueable wire as the guide to introduce an identical tube over it into the trachea. The epithelial integrity of the trachea was later examined histologically when the animals were sacrificed either immediately after the surgery or at 28 days post-surgery, depending on the corresponding research protocols., Results: Orotracheal intubation was successfully completed in all mice using either the Conventional (N = 42) or the Modified method (N = 50). With the Modified method, intubation took less time (1.73 vs. 2.17 min, Modified vs. Conventional, p < 0.001) and fewer attempts (1.0 vs. 1.33, p < 0.001), and there were fewer procedural difficulties (0% vs. 16.7%, p = 0.009) and complications (0% vs. 11.9%, p = 0.041) compared with the Conventional method. Histological analysis revealed a significantly lower incidence of immediate (0% vs. 39%, p < 0.001) and late (0% vs. 58%, p < 0.001) injuries to the tracheal epithelial lining with the Modified method compared to the Conventional method., Conclusions: Tracheal intubation for laboratory mice can be completed efficiently, safely and atraumatically using the proposed Modified method employing readily available inexpensive instruments.

The fabrication and characteristics of Ce/Cr-doped crystal fibers employing drawing tower technique are reported. The fluorescence spectrum of the Ce/Cr fibers at the core diameter ranging from 10 to 21 µm exhibited a 200-nm near-Gaussian broadband emission which enabled to provide an axial resolution of 1.8-μm and a power density of 79.1 nW/nm. The proposed broadband Ce/Cr-doped crystal fibers may be provided as a high-resolution light source for the use in optical coherence tomography system as well as industrial inspection and biomedical imaging applications.

Background: Infections of Echinococcus granulosus sensu stricto (s.s), E. multilocularis and E. shiquicus are commonly found co-endemic on the Qinghai-Tibet plateau, China, and an efficient tool is needed to facilitate the detection of infected hosts and for species identification., Methodology/principal Findings: A single-tube multiplex PCR assay was established to differentiate the Echinococcus species responsible for infections in intermediate and definitive hosts. Primers specific for E. granulosus, E. multilocularis and E. shiquicus were designed based on sequences of the mitochondrial NADH dehydrogenase subunit 1 (nad1), NADH dehydrogenase subunit 5 (nad5) and cytochrome c oxidase subunit 1 (cox1) genes, respectively. This multiplex PCR accurately detected Echinococcus DNA without generating nonspecific reaction products. PCR products were of the expected sizes of 219 (nad1), 584 (nad5) and 471 (cox1) bp. Furthermore, the multiplex PCR enabled diagnosis of multiple infections using DNA of protoscoleces and copro-DNA extracted from fecal samples of canine hosts. Specificity of the multiplex PCR was 100% when evaluated using DNA isolated from other cestodes. Sensitivity thresholds were determined for DNA from protoscoleces and from worm eggs, and were calculated as 20 pg of DNA for E. granulosus and E. shiquicus, 10 pg of DNA for E. multilocularis, 2 eggs for E. granulosus, and 1 egg for E. multilocularis. Positive results with copro-DNA could be obtained at day 17 and day 26 after experimental infection of dogs with larval E. multilocularis and E. granulosus, respectively., Conclusions/significance: The multiplex PCR developed in this study is an efficient tool for discriminating E. granulosus, E. multilocularis and E. shiquicus from each other and from other taeniid cestodes. It can be used for the detection of canids infected with E. granulosus s.s. and E. multilocularis using feces collected from these definitive hosts. It can also be used for the identification of the Echinococcus metacestode larva in intermediate hosts, a stage that often cannot be identified to species on visual inspection.

A p-i-n structure with near-UV(n-UV) emitting InGaN/GaN multiple quantum well(MQW) structure stacked on a green unipolar InGaN/GaN MQW was epitaxially grown at the same sapphire substrate. Photon recycling green light-emitting diodes(LEDs) with vertical-conduction feature on silicon substrates were then fabricated by wafer bonding and laser lift-off techniques. The green InGaN/GaN QWs were pumped with n-UV light to reemit low-energy photons when the LEDs were electrically driven with a forward current. Efficiency droop is potentially insignificant compared with the direct green LEDs due to the increase of effective volume of active layer in the optically pumped green LEDs, i.e., light emitting no longer limited in the QWs nearest to the p-type region to cause severe Auger recombination and carrier overflow losses.

We present a trichromatic GaN-based light-emitting diode (LED) that emits near-ultraviolet (n-UV) blue and green peaks combined with red phosphor to generate white light with a low correlated color temperature (CCT) and high color rendering index (CRI). The LED structure, blue and green unipolar InGaN/GaN multiple quantum wells (MQWs) stacked with a top p-i-n structure containing an InGaN/GaN MQW emitting n-UV light, was grown epitaxially on a single substrate. The trichromatic LED chips feature a vertical conduction structure on a silicon substrate fabricated through wafer bonding and laser lift-off techniques. The blue and green InGaN/GaN MQWs were pumped with n-UV light to re-emit low-energy photons when the LEDs were electrically driven with a forward current. The emission spectrum included three peaks at approximately 405, 468, and 537 nm. Furthermore, the trichromatic LED chips were combined with red phosphor to generate white light with a CCT and CRI of approximately 2900 and 92, respectively.

Background: Whether serum triglyceride level correlates with clinical outcomes of patients with ST segment elevation myocardial infarction (STEMI) treated by primary percutaneous coronary intervention (pPCI) remains unclear., Methods: From June 2008 to February 2012, all patients with STEMI who were treated with pPCI in this tertiary referral hospital and then had fasting lipid profiles measured within 24 hours were included and dichotomized into lower- (≦ 150 mg/dl) and higher-triglyceridemic (>150 mg/dl) groups. Baseline characteristics, in-hospital outcomes, and late major adverse cardiovascular events (MACE) were compared in-between. Independent predictors for in-hospital death and late adverse events were identified by multivariate logistic and Cox regression analyses., Results: A total of 247 patients were enrolled, including 163 lower-triglyceridemic and 84 higher-triglyceridemic subjects. The angiographic characteristics, pPCI results and in-hospital outcomes were similar between the two groups. However, multivariate logistic analysis identified triglyceride level as a negative predictor for in-hospital death (OR 0.963, 95% CI 0.931-0.995, p = 0.023). At follow-up for a mean period of 1.23 to 1.40 years, compared with the high-triglyceridemic group, low-triglyceridemic patients had fewer cumulative incidences of target vessel revascularization (TVR) (21.7% vs. 9.5%, p = 0.011) and overall MACE (26.1% vs. 11.9%, p = 0.0137). Cox regression analysis confirmed serum triglyceride as a negative predictor for TVR and overall MACE., Conclusions: Serum triglyceride level inversely correlates with in-hospital death and late outcomes in patients with STEMI treated with pPCI. Thus, when managing such patients, a high serum triglyceride level can be regarded as a benign factor but not a target for aggressive therapy.